Nonetheless, VCs from SARMs representing discontinuous SAR regions are also attractive candidates for compound design.
Importantly, the NBH-based mini-QSAR approach is only applicable to candidate compounds falling into SARMs that represent continuous SAR regions, as illustrated in Figure 6a.
By contrast, compounds falling into discontinuous SAR regions, as shown in Figure 6b, fall outside the applicability of standard QSAR modeling.
Continuous SAR regions are characterized by the presence of compounds with structural modifications that lead to gradual changes in potency, whereas discontinuous SAR regions contain structural analogs with large (and essentially unpredictable) potency variations.
The distribution of several known nuclear scaffold/matrix trans-factors or associated families within both the MAR and SAR regions was assessed in silico and compared with that observed in the loop fraction.
In benchmark calculations on six different sets of G protein-coupled receptor ligands, potency values of subsets of test compounds falling into continuous local SAR regions were accurately predicted using the NBH-based approach, and prediction accuracy generally increased with the number of qualifying NBHs.
a Original SAR image region.
c Labeling the SAR image region in pixel.
b Labeling the SAR image region in grid of 5 ×5 cells.
In b and c, we use red for UA, green for WL, and blue for WB, as an overlay on the SAR image region.
Studies conducted exclusively in Hong Kong special administrative region (SAR), Macao SAR or Taiwan, China, were excluded.
